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Research and Reviews: A Journal of Pharmaceutical Science Review Article

Comprehensive Review of Kojic Acid and Its Derivatives: Biological Activities, Safety, and Therapeutic Potential in Depigmentation

  1. Sejal Rajendra Chaudhari Department of Pharmaceutics, P. S. G. V. P. Mandal’s College of Pharmacy, Shahada
  2. Sunila A. Patil Department of Pharmaceutical Chemistry, P. S. G. V. P. Mandal’s College of Pharmacy, Shahada
  3. Amuruta N. Patil Department of Pharmaceutical Chemistry, P. S. G. V. P. Mandal’s College of Pharmacy, Shahada
  4. S. P. Pawar Department of Pharmacy, P. S. G. V. P. Mandal’s College of Pharmacy, Shahada

Abstract

There are several uses for kojic acid in human medicine, particularly in depigmentation. Additionally, derivatives of it are suggested to enhance efficacy, avoid side effects, and stop chemical degradation. With an eye toward human use and an attempt to clarify the action mechanisms, the goal of this study was to review the most recent scientific literature regarding the biological activities and safety information of kojic acid or its derivatives. During the evaluation of three distinct databases, the terms “toxicity,” “adverse effect,” “efficacy,” “effect,” “activity,” and “safety” were crossed with the word “kojic.” Articles were chosen based on predetermined standards. In addition to its depigmenting properties, kojic acid and its derivatives have antitumor properties and can function as antioxidants, antimicrobials, anti-inflammatories, radioprotectors, anticonvulsants, and agents for managing obesity. Following cell penetration, the molecules bind to the active site of tyrosinase, regulating factors involved in melanogenesis, modulating leucocytes, and scavenging free radicals, which results in depigmenting activity. As a result, ligands, size, and polarity all play significant roles in activity. Certain cancerous cell lines, such as those from melanoma, ovarian, breast, colon, and hepatocellular carcinomas, are susceptible to the cytotoxicity of kojic acid and its derivatives. In terms of safety, at the tested concentrations, kojic acid or its derivatives are safe compounds for human use. Applications in medicine, pharmacology, and cosmetics could benefit greatly from kojic acid and its derivatives.

Keywords

References (19)

  1. Lage D, Costa A. Melasma. In: Costa A, editor. Tratado Internacional de Cosmecêuticos. Rio de Janeiro: Guanabara Koogan; 2012. p. 533–540.
  2. Zaid AN, Al Ramahi R. Depigmentation and Anti-aging Treatment by Natural Molecules. Current Pharmaceutical Design. 2019;25(20):2292-2312. doi:10.2174/1381612825666190703153730
  3. Meybeck A, inventor; LVMH Recherche GIE, assignee. Pharmaceutical or cosmetic composition containing hydroquinone and kojic acid. United States patent US 5,279,834. 1994.
  4. Aytemir M, Ozcelik B, Orhan IE, Karakaya G, Senol FS, inventors. Kojic acid-derived Mannich bases with biological effect. United States patent US 9,975,884. 2018.
  5. Piršelová K, Baláž Š, Ujhelyová R, Šturdík E, Veverka M, Uher M, et al. Quantitative Structure‐Time‐Activity Relationships (QSTAR): Growth Inhibition of Escherichia coli by Nonionizable Kojic Acid Derivatives. Quantitative Structure-Activity Relationships. 1996;15(2):87-93. doi:10.1002/qsar.19960150202
  6. Khezri K, Saeedi M, Morteza-Semnani K, Akbari J, Hedayatizadeh-Omran A. A promising and effective platform for delivering hydrophilic depigmenting agents in the treatment of cutaneous hyperpigmentation: kojic acid nanostructured lipid carrier. Artificial Cells, Nanomedicine, and Biotechnology. 2021;49(1):38-47. doi:10.1080/21691401.2020.1865993
  7. Roselan MA, Ashari SE, Faujan NH, Mohd Faudzi SM, Mohamad R. An Improved Nanoemulsion Formulation Containing Kojic Monooleate: Optimization, Characterization and In Vitro Studies. Molecules. 2020;25(11):2616. doi:10.3390/molecules25112616
  8. Ezzat H, Rady M, Hathout RM, Abdel-Halim M, Mansour S. Enhanced anti-bacterial effect of kojic acid using gelatinized core liposomes: A potential approach to combat antibiotic resistance. Journal of Drug Delivery Science and Technology. 2021;64:102625. doi:10.1016/j.jddst.2021.102625
  9. Kolbe L, Mann T, Gerwat W, Batzer J, Ahlheit S, Scherner C, et al. 4‐n‐butylresorcinol, a highly effective tyrosinase inhibitor for the topical treatment of hyperpigmentation. Journal of the European Academy of Dermatology and Venereology. 2012;27(s1):19-23. doi:10.1111/jdv.12051
  10. Lajis AFB, Hamid M, Ariff AB. Depigmenting Effect of Kojic Acid Esters in Hyperpigmented B16F1 Melanoma Cells. Journal of Biomedicine and Biotechnology. 2012;2012:1-9. doi:10.1155/2012/952452
  11. Gonçalez ML, Marcussi DG, Calixto GMF, Corrêa MA, Chorilli M. Structural Characterization andIn VitroAntioxidant Activity of Kojic Dipalmitate Loaded W/O/W Multiple Emulsions Intended for Skin Disorders. BioMed Research International. 2015;2015:1-8. doi:10.1155/2015/304591
  12. Lobato CC, Ordoñez ME, Queiroz RL, Santos CBR, Borges RS. A comparative study between kojic acid and its methylated derivatives as antioxidant related to maltol and alomaltol. Chemical Data Collections. 2020;28:100464. doi:10.1016/j.cdc.2020.100464
  13. Wei X, Du L, Sun L, Wang C, Song F, Qian H, et al. Kojic acid enhances the proliferation of human corneal epithelial cells via p38 and p21 signaling pathways. European Journal of Ophthalmology. 2020;31(5):2287-2293. doi:10.1177/1120672120962065
  14. Wei X, Luo D, Yan Y, Yu H, Sun L, Wang C, et al. Kojic acid inhibits senescence of human corneal endothelial cells via NF-κB and p21 signaling pathways. Experimental Eye Research. 2019;180:174-183. doi:10.1016/j.exer.2018.12.020
  15. Aytemir MD, Çalış Ü. Anticonvulsant and Neurotoxicity Evaluation of Some Novel Kojic Acids and Allomaltol Derivatives. Archiv der Pharmazie. 2010;343(3):173-181. doi:10.1002/ardp.200900236
  16. Wang K, Liu C, Di CJ, Ma C, Han CG, Yuan MR, et al. Kojic Acid Protects C57BL/6 Mice from Gamma-irradiation Induced Damage. Asian Pacific Journal of Cancer Prevention. 2014;15(1):291-297. doi:10.7314/apjcp.2014.15.1.291
  17. Phasha V, Senabe J, Ndzotoyi P, Okole B, Fouche G, Chuturgoon A. Review on the Use of Kojic Acid—A Skin-Lightening Ingredient. Cosmetics. 2022;9(3):64. doi:10.3390/cosmetics9030064
  18. Syed Azhar SNA, Ashari SE, Ahmad S, Salim N. In vitro kinetic release study, antimicrobial activity and in vivo toxicity profile of a kojic acid ester-based nanoemulsion for topical application. RSC Advances. 2020;10(71):43894-43903. doi:10.1039/d0ra04807k
  19. Chaudhari U, Nemade H, Sureshkumar P, Vinken M, Ates G, Rogiers V, et al. Functional cardiotoxicity assessment of cosmetic compounds using human-induced pluripotent stem cell-derived cardiomyocytes. Archives of Toxicology. 2017;92(1):371-381. doi:10.1007/s00204-017-2065-z
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